Glaucoma is the leading cause of irreversible blindness in the world. Due to its potential to cause permanent vision loss, it is important to understand how systemic conditions and their respective ...treatments can be associated with or increase the risk for developing glaucoma. In this review, we examined the literature for up-to-date discussions and provided commentary on glaucoma, its pathophysiology, and associated risk factors. We discuss systemic diseases and the impact, risk, and mechanism for developing glaucoma, including pharmacologically induced glaucoma; inflammatory and auto-immune conditions; infectious, dermatologic, cardiovascular, pulmonary, renal, urologic, neurologic, psychiatric and systemic malignancies: intraocular tumors; as well as pediatric, and genetic conditions. The goal of our discussion of systemic conditions including their commonality, mechanisms, treatments, and associations with developing glaucoma is to emphasize the importance of ocular examinations and follow-up with the multidisciplinary teams involved in the care of each patient to prevent unnecessary vision-loss.
In this work, we compute the number of
n
,
k
d
stabilizer codes made up of
d
-dimensional qudits, for arbitrary positive integers
d
. In a seminal work by Gross \cite{Gross2006} the number of
n
...,
k
d
stabilizer codes was computed for the case when
d
is a prime (or the power of a prime, i.e.,
d
=
p
m
, but when the qudits are Galois-qudits). The proof in \cite{Gross2006} is inapplicable to the non-prime case. For our proof, we introduce a group structure to
n
,
k
d
codes, and use this in conjunction with the Chinese remainder theorem to count the number of
n
,
k
d
codes. Our work overlaps with \cite{Gross2006} when
d
is a prime and in this case our results match exactly, but the results differ for the more generic case. Despite that, the overall order of magnitude of the number of stabilizer codes scales agnostic of whether the dimension is prime or non-prime. This is surprising since the method employed to count the number of stabilizer states (or more generally stabilizer codes) depends on whether
d
is prime or not. The cardinality of stabilizer states, which was so far known only for the prime-dimensional case (and the Galois qudit prime-power dimensional case) plays an important role as a quantifier in many topics in quantum computing. Salient among these are the resource theory of magic, design theory, de Finetti theorem for stabilizer states, the study and optimisation of the classical simulability of Clifford circuits, the study of quantum contextuality of small-dimensional systems and the study of Wigner-functions. Our work makes available this quantifier for the generic case, and thus is an important step needed to place results for quantum computing with non-prime dimensional quantum systems on the same pedestal as prime-dimensional systems.
There is an urgent need to identify biomarkers of early response that can accurately predict the benefit of immune checkpoint inhibitors (ICI). Patients receiving durvalumab/tremelimumab had tumor ...samples sequenced before treatment (baseline) to identify variants for the design of a personalized circulating tumor (ctDNA) assay. ctDNA was assessed at baseline and at 4 and/or 8 weeks into treatment. Correlations between ctDNA changes to radiographic response and overall survival (OS) were made to assess potential clinical benefit. 35/40 patients (87.5%) had personalized ctDNA assays designed, and 29/35 (82.9%) had plasma available for baseline analysis, representing 16 unique solid tumor histologies. As early as 4 weeks after treatment, decline in ctDNA from baseline predicted improved OS (P = 0.0144; HR = 9.98) and ctDNA changes on treatment‐supported and refined radiographic response calls. ctDNA clearance at any time through week 8 identified complete responders by a median lead time of 11.5 months ahead of radiographic imaging. ctDNA response monitoring is emerging as a dynamic, personalized biomarker method that may predict survival outcomes in patients with diverse solid tumor histologies, complementing and sometimes preceding standard‐of‐care imaging assessments.
We used a novel approach combining a tissue‐informed comprehensive genomic profiling assay with personalized blood‐based monitoring demonstrating that early ctDNA dynamics predict long‐term clinical outcomes in patients with different solid tumors treated with immune checkpoint inhibition. Molecular response as measured by ctDNA change from baseline represents an important emerging tool for assessing drug effect, complementary to imaging‐based response assessment.
To present an uncommon cause of intermittent angle closure in a young adult patient presenting with intermittent headache and blurry vision exacerbated by accommodation.
A 37-year-old man reported ...experiencing intermittent blurry vision, headache, and pain in both eyes associated with prolonged periods of reading beginning at age 17. Serial intraocular pressure (IOP) measurements showed an increase in IOP from 14 to 32 mmHg in the right eye and from 9 to 37 mmHg in the left eye after 145 minutes of sustained accommodation while sitting up. IOP did not normalize after laser peripheral iridotomy but did normalize after clear lens extraction.
This case characterized a rare presentation of accommodation-induced IOP elevation in a young adult male that resolved only after clear lens extraction. The clinical takeaway was the importance of considering accommodation-associated angle closure in patients presenting with high intraocular pressures, eye strain, and/or headache with accommodative activities. Notable symptoms that should raise suspicion for this syndrome include halos, changes in visual acuity, and headache with accommodation. We suggested that patients presenting with these symptoms be followed closely, with a full glaucoma evaluation including gonioscopy and possible ultrasound biomicroscopy to assess for pediatric eversional angle closure with headache, plateau iris, angle closure glaucoma, and lens-induced angle closure.
BackgroundSpine pain is one of the most common conditions seen in primary care and is often treated with ineffective, aggressive interventions, such as prescription pain medications, imagery and ...referrals to surgery. Aggressive treatments are associated with negative side effects and high costs while conservative care has lower risks and costs and equivalent or better outcomes. Despite multiple well-publicised treatment guidelines and educational efforts recommending conservative care, primary care clinicians (PCCs) widely continue to prescribe aggressive, low-value care for spine pain.MethodsIn this qualitative study semistructured interviews were conducted with PCCs treating spine pain patients to learn what prevents clinicians from following guidelines and what tools or support could promote conservative care. Interviews were conducted by telephone, transcribed and coded for thematic analysis.ResultsForty PCCs in academic and private practice were interviewed. Key reflections included that while familiar with guidelines recommending conservative treatment, they did not find guidelines useful or relevant to care decisions for individual patients. They believed that there is an insufficient body of real-world evidence supporting positive outcomes for conservative care and guidance recommendations. They indicated that spine pain patients frequently request aggressive care. These requests, combined with the PCCs’ commitment to reaching shared treatment decisions with patients, formed a key reason for pursuing aggressive care. PCCs reported not being familiar with risk-screening tools for spine patients but indicated that such screens might increase their confidence to recommend conservative care to low-risk patients.ConclusionsPCCs may be more willing to give conservative, guideline-consistent care for spine pain if they had tools to assist in making patient-specific evaluations and in countering requests for unneeded aggressive care. Such tools would include both patient risk screens and shared decision-making aids that include elements for resolving patient demands for inappropriate care.
BackgroundOncolytic viruses have emerged as promising therapeutic agents to selectively infect and destroy cancer cells while synergizing with checkpoint inhibitors to increase efficacy of ...immunotherapy. IVX037 is a novel bio-selected, receptor targeted, non-genetically modified, naturally occurring oncolytic strain of a human enteric RNA picornavirus. It is a non-enveloped, single-positive-stranded RNA virus with a capsid diameter of ~25nm. IVX037 challenge can induce selective in vitro tumor cell lytic infection via specific viral capsid cellular receptor interactions in cell cultures of human colorectal, gastric and ovarian cancers. Significant anti-tumor activity was displayed by a single intratumoral injection of IVX037 in human xenografts of microsatellite stable (MSS) -colorectal, gastric and ovarian cancers in SCID mice. In vivo human MSS colorectal cancer xenograft studies in mice, revealed that intratumoral administration of IVX037 induced elevated levels of gamma-INF response genes (CXCL10, RIG-I) and up-regulated expression of a key immune-checkpoint molecule, PD-L1, indicating an inflammation phenotype within the treated tumor microenvironment (TME). The induction of a virally inflamed TME is suggested to potentially allow increased migration of anti-tumor lymphocytes both within injected and distant lesions and elevated levels of cellular targets for immune checkpoint therapies.MethodsThis is a Phase 1a, first-in-human, open-label, non-randomized, multi-center clinical trial of intratumoral IVX037 in patients with advanced MSS colorectal , gastroesophageal or ovarian cancer. Patients (pts) must have one injectable tumour of liver/nodal/peritoneal disease. Pts will be sequentially enrolled into 3 dose escalation cohorts to receive 1 (n=3 pts), 2 (n=3 pts) or 3 (n=15 pts) doses of up to 3 x 108 TCID50 of IVX037 intratumorally, administered on Days 1, 15 and 29 of Cycle 1, as applicable. The primary objective is to determine the feasibility, safety and tolerability of intratumoral IVX037 including the incidence of dose-limiting toxicities (DLT). The secondary objective is to assess the maximum tolerated dose (MTD) of IVX037, administered as either 1, 2 or 3 injections per lesion. Tumor response will be assessed using RECIST 1.1, with the first response assessment occurring at Day 50. Several biomarker effects of IVX037 administration in peripheral blood and tumor tissue addressing tumor infiltrating lymphocytes and cellular target expression levels for immune checkpoint therapies will be assessed.
Abstract Background context Back and neck problems are among the most common medical symptoms in the general US population, they generate substantial direct and indirect costs, and there is ...substantial variation in care provided to treat such conditions. Purpose To brainstorm methods to improve the value of healthcare services provided to patients with spine related disorders. Setting The 2015 North American Spine Society Annual Meeting in Chicago where a group of providers, insurers, employers, advocates, and researchers convened to discuss ways to improve the value of healthcare services provided to patients with spine related disorders. Methods Guided by the Institute of Medicine's six aims of care (safe, effective, patient-centered, timely, efficient, and equitable care), the group surfaced several evidence-based opportunities for improving value. Results The opportunities centered on four themes: the need to develop commonly-defined groupings of spine pain patients to ensure fair comparisons of healthcare value; ways to address current misuse of care providers through improved protocols; the need to avoid patient harms including unnecessary risk exposure, disability labeling, and overuse of opioid drug prescriptions; and the need to establish and use, on a broad scale, methods to learn from actual patient care experiences. Conclusions These themes lend themselves to several obvious long-term interventions – identification and establishment of better specified treatment guidelines targeting specific groups of patients, integration of primary spine care providers who do not prescribe addictive medications as a first line treatment, and establishment of registries. The convergence of accelerating and divergent resource consumption for its treatment, widespread use of new delivery and payment methods designed to improve outcomes and curtail the rise in healthcare costs, and availability of technologies that can facilitate data collection, analysis, and learning provide a rich opportunity to improve the value of healthcare delivery for spine pain.
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